Depression

Question 1

major unipolar depression is one of the most common mood disorders, characterized by ______ mood (absence of happiness), _____, ____ and desperation, loss of ___, _____, _____, appetite, and _____, difficulty in ____ and ____ ____.

Answer 1

unhappy, worthlessness, guilt, interest, energy, motivation, pleasure, concentration, restless agitation

Question 2

depressive episodes that are triggered by external events

Answer 2

reactive

Question 3

when depressive episodes occur without apparent cause

Answer 3

endogenous

Question 4

depression is considered pathological when symptoms are ____ or _____. There is high comorbidity of depression with other medical conditions such as ___ and ____ _____. Symptom clusters vary with individuals and there may be depression ______ associated with distinct causes and pathophysiologies

Answer 4

prolonged, disproportionate, anxiety, alcohol dependence, subtypes

Question 5

Depression increases risk of suicide by ____%

Answer 5

7-15

Question 6

Unipolar depression typically alternates with ____ states, and episodes last up to _____ months. Episodes can recur through life, often increasing in ____ and _____. Sometimes, depressive episodes can end on their own.

Answer 6

normal, 6-9, frequency, intensity

Question 7

______% of the population is affected by depression. ____ are more likely to be diagnosed and incidence often coincides with major ____ changes such as post partum and ____. The incidence of depression has ____ over the last 50 years, and the age of onset has ______. Some types of depression may have a ____ influence, while others less so

Answer 7

15-20, women, hormonal, menopause, increased, decreased, genetic

Question 8

Depression is viewed as a _____ disorder, and is closely related with anxiety. Intense stress and anxiety often ____ depression.

Answer 8

stress-linked, precede

Question 9

Some forms of depression may be linked to alterations in the _______ and higher _____ and ____ levels.

Answer 9

HPA-axis, cortisol, CRF

Question 10

a stress related peptide transmitter in the brain that affects numerous limbic brain regions and stimulates cortisol release

Answer 10

CRF

Question 11

People with ____ ____, which is associated with high levels of glucocorticoids, are more prone to depression

Answer 11

cushing’s syndrome

Question 12

Circulating levels of ____ tend to be higher in depressed subjects vs other disorders and controls.

Answer 12

CORT

Question 13

a synthetic glucocorticoid that can suppress cortisol release in normal people

Answer 13

dexamethasone

Question 14

Dexamethasone can “fool” the HPA axis into believing there are ____ levels of cortisol than normal. Through ____ ____, levels of cortisol drop in healthy control, but not in depressed patients. This is called the _____ _____ ____

Answer 14

higher, negative feedback, dexamethasone suppression test

Question 15

functional imaging studies show increased blood flow / ____ utilization by the ___ and ______. Increased amygdala activity is associated with ____ that may contribute to stress / depressive symptoms. Some aspects of depression may be caused by disrupted regulation of amygdala ___ _____ by the PFC. It may be one mechanism underlying aberrant negative ____ of life events

Answer 15

O2, amygdala, vmPFC, anxiety, emotional processing, appraisals

Question 16

Alterations in brain activity can be normalized with ______ treatment. These regions receive dense _____ and _____ input.

Answer 16

antidepressant, noradrenergic, serotonergic

Question 17

Reduced ____ volumes have also been observed in those with depression

Answer 17

hippocampal

Question 18

model of depression that focuses on the stress-related neuro-endocrine abnormalities of depression

Answer 18

glucocorticoid hypothesis

Question 19

Hypothalamic CRF neurons are regulated by other nuclei: the amygdala ____ it, while the _____ inhibits it. Early life stress can increase CRF expression in the ______, increase amygdala _____ to stress, and decrease ______ ____ in the hippocampus

Answer 19

stimulates, hippocampus, hypothalamus, sensitivity, glucocorticoid receptors

Question 20

Glucocorticoids increase hippocampal ______, and high, _____ levels of intense stress can cause _____ of hippocampal and ____ neurons.

Answer 20

excitability, prolonged, atrophy, PFC

Question 21

impaired hippocampal function leads to the loss of _____ regulation of the HPA axis. It may also contribute to the behavioural syndrome in depression where patients often report being unable to ____ a time when they were happy. Antidepressant drugs reduce ____ levels and reverse loss of hippocampal _______ in animal studies

Answer 21

inhibitory, remember, CRF, dendrites

Question 22

Many animal depression models involve repeated, _____ stressors.

Answer 22

uncontrollable

Question 23

when rodents are exposed to different types of stressors such as cold temperatures, wet bedding, restraint, and sudden loud noise over 1-3 weeks to they cannot habituate to one form of stress

Answer 23

chronic mild stress

Question 24

when an intruder rat or mouse fights a more dominant conspecific - repeated experiences with defeat can induce depression

Answer 24

chronic social defeat

Question 25

when young animals are separated from their mothers for brief periods daily during the first few weeks of life

Answer 25

early maternal separation

Question 26

Forced swim tests in rats or tail-suspension tests in mice model behavioural ______, as ____ is thought to reflect a ____ coping strategy. Acute antidepressant treatment reduces immobility and increases active coping strategies such as ____ and ____ in normal animals

Answer 26

despair, immobility, passive, swimming, climbing

Question 27

typically used with the social defeat model, where rodents avoid conspecifics after repeated defeats

Answer 27

social avoidance

Question 28

a behavioural test for depression that models anhedonia - depression reduces preference for sucrose solution vs water; chronic antidepressants can reverse this effect

Answer 28

sucrose preference

Question 29

Behavioural tests are routinely used as screens for ____ antidepressants. However, they do not totally translate to ___ observed in human patients. For example, depressed patients still ____ sweet foods if it is presented in front of them, but are less likely to work to obtain them

Answer 29

novel, deficits, like

Question 30

Early life stressors can make the HPA axis ______ and increase risk for depression in adult animals. Adults rats subjected to early life trauma showed higher stress-induced ____ and ____ release as adults, and greater ____ behaviours. Antidepressant treatment prevents this increase in adults and _____ the behaviours. When treatment was terminated, all the abnormalities _____

Answer 30

over-responsive, CRF, cortisol, depressive-like, prevents, returned

Question 31

in the 1950s-60s, _____ a drug that reduces monoamine levels, was found to induce depression. The first ___ _____ _______, which block metabolism of monoamines and increase brain levels, _____ depression. The first tricyclic antidepressant ______, which blocks monoamine reuptake was also found to be effective. In the 1980s, _____ (SSRI) was found to be effective at treating depression. All of these findings support the ______ hypothesis

Answer 31

reserpine, monoamine oxidase inhibitors, alleviate, imipramine, fluoxetine, monoamine

Question 32

the hypothesis that depression is the rsult of abnormal reduction in brain monoamine (mostly 5-HT and NE) levels

Answer 32

monoamine hypothesis of depression

Question 33

Some limitations of the monoamine hypothesis are that antidepressants increase monoamine levels ____ yet there is a long lag between the drug treatment and the ____ of symptoms. Thus therapeutic effects may be mediated by longer lasting changes in ___/____ activity and their effects on _____ targets induced by repeated antidepressant treatment (rather than acute increases in NT release). Additionally, not all depressed patients ____ to drugs that increase monoamine levels. antidepressants tend to improve symptoms vs a placebo in more ______ depressed patients, but otherwise there is a large ____ effect. Additionally, depletion of ______ or ____ does not cause a depressive ____ in animal models. These animals instead show some behaviours that may loosely be related to depression such as _____, ______, hypersensitivity to ____ and altered patterns of ____ and ____.

Answer 33

quickly, alleviation, NE, 5-HT, postsynaptic, respond, severely, placebo, NE, 5-HT, phenotype, irritability, aggression, pain, feeding sleep

Question 34

another limitation of the monoamine hypothesis is that _____ ______ induces symptoms of depression in unmedicated depressed patients in ____, or healthy subjects with a ____ ___ of depression, but not in healthy subjects without that history. This means merely having low levels of serotonin does not cause depression, except in ____ individuals

Answer 34

tryptophan depletion, remission, family history, vulnerable

Question 35

Although the monoamine hypothesis is overly simple, ___ continues to be a focus because of its influence on ____ ____, _____, and response to _____ and _____ events.

Answer 35

5-HT, pain sensitivity, emotionality, positive, negative

Question 36

suicide victims and depressed patients show lower _____ _____ and ____ levels taken from post-mortem brains or _____ /______, which is indicative of lower 5-HT activity.

Answer 36

5-HT metabolite, precursor, blood, CSF

Question 37

polymorphisms in the _____ gene (short and long) can contribute to depression. The ____ allele is associated with reduced _____ function and ____ levels of 5-HT. These higher levels may reduce firing of 5-HT neurons via _______ inhibition. This may be linked to some forms of depression brought on by ______. Mutant mice _____ for the SERT gene (ie. only having ___ copy of the gene that reduces expression), have lower _____ 5-HT neuron firing rate.

Answer 37

SERT, short, transporter, higher, autoreceptor-mediated, stress, heterozygous, 1, raphe

Question 38

_____ depressed individuals show increases in postsynaptic _____ receptors, which may be compensatory to ____ 5-HT activity. Chronic antidepressant treatment ______ the same receptors, in animal and human studies

Answer 38

unmedicated, 5-HT2, low, down-regulates

Question 39

In ____ studies, the magnitude of a biological response to 5-HT _____ or ____ is measured. Depressed patients show reduced _____ to 5-HT agonists, and this can be reversed with chronic ______ treatment.

Answer 39

challenge, agonist, antagonist, sensitivity, antidepressant

Question 40

acute SSRI treatment increases 5-HT by blocking ____. This in turn, activates ______ _____ to slow cell firing and reduces 5-HT release. Long-term SSRI treatment ______ autoreceptors, so these drugs can increase ______ 5-HT release. For example, ______ _____ autoreceptors become less sensitive to activation following chronic _____ treatment. Repeated SSRI treatment can also increase sensitivity of certain postsynaptic 5-HT receptors in the ____ and _____

Answer 40

reuptake, somatodendritic autoreceptors, down-regulates, synaptic, somatodendritic 5-HT1A fluoxetine, PFC, hippocampus

Question 41

NE plays a key role in ____ function, reward ______, _____/_____, and the ____ response. Results of NE _____ and _____ studies of depressed patients show have been inconsistent. One consistent finding is that untreated depressed patients show increased _____ receptors which may attenuate NE release

Answer 41

neuroendocrine, mechanisms, attention, arousal, stress, metabolite, receptor, alpha-2

Question 42

Chronic (_____ day) antidepressant treatment in animals downregulates postsynaptic ____ receptors and _____ _______. This lag parallels the onset of the ______ _______. However, this downregulation is not always seen in treated patients

Answer 42

7-21, beta, alpha autoreceptors, therapeutic response

Question 43

There are anatomic and functional interactions between NE neurons in the ____ and the 5-HT neurons in the _____, such that drugs that affect one system can affect the other.

Answer 43

LC, raphe

Question 44

There is renewed interest in how DA ______ may contribute to depression symptoms, particularly ______ (reduced motivation). _____ ______ ____ are being developed with consideration to not be habit forming like _____

Answer 44

dysfunction, anergia, triple-monoamine uptake blockers, cocaine

Question 45

double-blind, placebo controlled trials show that no one drug is more ____ than any other. There is also no way to ____ how a patient will respond to a particular drug. Each patient typically undergoes ____ to find a drug that optimally balances therapeutic vs ____ ___. All drugs require _____ administration and clinical effects depend on _____ changes that takes time to develop

Answer 45

effective, predict, trials, side effects, chronic, neural

Question 46

_____/ ____ therapy can be just as effective as antidepressants, although it takes longer, and when used in combination with drugs is even more effective

Answer 46

cognitive, behavioural

Question 47

certain drugs, primarily _____, are associated with increased risk of ____ in children and adolescents, but the causal relationship is unclear,

Answer 47

SSRIs, suicide

Question 48

first class of drugs used to treat depression; increases the amount of transmitter available for release within hours, but antidepressant effects require weeks of treatment

Answer 48

MAO inhibitors

Question 49

examples of MAO inhibitors include _____ (Nardil) _____, (marplan) and _____ (parnate). The use of MAO inhibitors are now limited due to multiple side effects such as _____ disturbances, ___ gain, increase in ____ ___, interaction with other _____ medications, and naturally occurring _____, which can augment NE release and cause dangerous increase in BP. MAO inhibitors also target other _____ ____ that metabolize other drugs

Answer 49

phenelzine, isocarboxazid, tranylcypromine, sleep, weight, blood pressure, cold, tyramine, liver enzymes

Question 50

antidepressants that block presynaptic transporters to inhibit reuptake of monoamines, which prolongs the duration of transmitter action at the synapse

Answer 50

tricyclic antidepressants

Question 51

Different tricyclic antidepressants have different _____ and ____ reuptake blocking properties. Examples are ____, ____ and _____. Side effects of TCAs include the blocking of ___ receptors, which causes ____ and fatigue, its _____ effects, which causes ___ ___, constipation, urine retention, ____, ____, impaired ____, and ___ ____. Some TCAs also block _____ _____ receptors, and when combined with NE reuptake blocking, may lead to potentially dangerous _____ effects such as ___, ____ and _____. Overdose can cause _____ and ____ depression, _____, convulsions, ____ ___ and coma. TCAs also have a low ____ _____, meaning fatalities occur at approximately ___x the normal therapeutic dose.

Answer 51

NE, 5-HT, amitriptyline, desipramine, imipramine, histamine, sedation, anticholinergic, dry mouth, dizziness, confusion, memory, blurred vision, alpha-1 adrenergic, cardiovascular, tachycardia, hypotension, arrhythmia, cardiovascular, respiratory, delirium, cardiac arrest, therapeutic index, 10

Question 52

2nd generation antidepressants that are most commonly prescribed, as the side effect profile is typically better than 1st generation drugs

Answer 52

SSRIs

Question 53

The therapeutic effect of SSRIs is mediated by increased activation of some 5-HT receptors. Activation of other receptors can lead to _____, _____ disorders, _____, ____ and ____ dysfunction.

Answer 53

anxiety, movement, insomnia, headaches, sexual

Question 54

dangerous effects when SSRIs combined with other 5-HT agonists or drugs that interfere with SSRI metabolism

Answer 54

serotonin syndrome

Question 55

serotonin syndrome can lead to ____, ____, _____, ____, fever, ____, diarrhea, increased ___ ____ and ______ ______.

Answer 55

agitation, disorientation, ataxia, spasms, shivering, heart rate, blood pressure

Question 56

SSRIs can cause physical ______ and ____ that can last several weeks. This results in ____, ____ vivid ____, increased ____, ____ and _____

Answer 56

dependence, withdrawal, fatigue, insomnia, dreams, anxiety, agitation, irritability

Question 57

ketamine is a _____ _____ antagonist. At ______ doses through _____, there is rapid reduction in depressive symptoms for _____% of treatment ______ patients (after psychosis dissipates). Effects last for _____ weeks, and an _____ formula has recently been approved.

Answer 57

non-competitive, NMDA, sub-anaesthetic, IV, 7, resistent, 1-3, intra-nasal

Question 58

The mechanism of ketamine appears to be driven by increased ______. It can potentiate ____ receptor function, potentially by increasing ____ and _____ release in the PFC. Administration of ____ ____ ____ prevents the antidepressant response to ketamine in animal models. Ketamine also induces multiple forms of ___ ___ via activation of multiple ___ ___ with effects persisting after acute effects have worn off. Ketamine ____ may also contribute to antidepressant effects

Answer 58

excitation, AMPA, glutamate, DA, AMPA receptor antagonists, synaptic plasticity, signalling cascades, metabolites

Question 59

characterized by periods of depression alternating with mania

Answer 59

bipolar disorder

Question 60

symptoms of mania include inflated __ _____, reduced need for ____, flight of ____, ______, increased ____ ___ activity, but rarely completed tasks. When mania subsides, difficulties related to behaviour due to mania can trigger bouts of ______.

Answer 60

self esteem, sleep, ideas, distractibility, goal directed, depression

Question 61

the cycling ____ of bipolar disorder varies, but rapid cycling consists of ___ or more cycles in one year. Some may cycle several times in one _____. Mania rarely occurs _____.

Answer 61

rate, 4, day, alone

Question 62

a milder form of bipolar disorder in which patients cycle between dysthymia (milder depression) and hypomania (increased energy)

Answer 62

cyclothymia

Question 63

incidence of mania is considerably ____ than depression. There is a _______% higher prevalence in the U.S. and men and women are affected _____

Answer 63

lower, 1-4, equally

Question 64

The neural basis of mania is poorly understood, but may involve pathology of the ____ and ____

Answer 64

hippocampus, amygdala

Question 65

the most effective medication for patients with bipolar disorder

Answer 65

lithium carbonate

Question 66

lithium carbonate eliminates / reduces ____ episodes without causing depression or producing _____. it has no effect in ____ individuals. It takes ___ weeks for maximal effects to emerge and is particularly effective in reducing ____ in bipolar individuals. Lithium elevates brain _____ _____ levels, and increases _____ ____. At the same time, it reduces ______ activity by enhancing _____ and reducing ____. Lithium likely modifies _____ ___ at points beyond the transmitter receptors (ie. second messenger systems).

Answer 66

manic, sedation, healthy, 2-3, suicide, tryptophan 5-HT, 5-HT release, catecholamine, reuptake, release, synaptic transmission

Question 67

the side effects of lithium are generally mild but include increased ___, ____, impaired ___ and ____, fatigue, ____ and ____ gain. Higher levels can be ____ and occur when plasma ____ levels are lower. The ____ ___ is low and thus blood levels of lithium must be ____ regularly.

Answer 67

thirst, urination, concentration memory, tremor, weight, toxic, Na+, therapeutic index, monitored